Antifungal immunity

Zymosan is a yeast cell wall component that is recognized by various pattern recognition receptors. In mouse models, zymosan induces skin inflammation and arthritis. Nitric oxide (NO) and chemoattractants, such as leukotriene B4 (LTB4), are implicated in inducing neutrophil migration to sites of inflammation. Hyperactivation of this inflammatory response underlies some diseases associated with fungal infection. Takahashi et al. found that neutrophil recruitment to zymosan in mice deficient in the pattern recognition receptor CD300b was impaired compared to that in wild-type mice. Furthermore, inflammatory dendritic cells produced NO in response to zymosan and stimulated neutrophil recruitment in a CD300b-dependent manner. The authors identified phytosphingosine, a lipid component of zymosan, as a potential CD300b ligand, which suggests that this interaction may contribute to antifungal immune responses.

Abstract

Zymosan is a glucan that is a component of the yeast cell wall. Here, we determined the mechanisms underlying the zymosan-induced accumulation of neutrophils in mice. Loss of the receptor CD300b reduced the number of neutrophils recruited to dorsal air pouches in response to zymosan, but not in response to lipopolysaccharide (LPS), a bacterial membrane component recognized by Toll-like receptor 4 (TLR4). An inhibitor of nitric oxide (NO) synthesis reduced the number of neutrophils in the zymosan-treated air pouches of wild-type mice to an amount comparable to that in CD300b−/− mice. Treatment with clodronate liposomes decreased the number of NO-producing, CD300b+ inflammatory dendritic cells (DCs) in wild-type mice, thus decreasing NO production and neutrophil recruitment. Similarly, CD300b deficiency decreased the NO-dependent recruitment of neutrophils to zymosan-treated joint cavities, thus ameliorating subsequent arthritis. We identified phytosphingosine, a lipid component of zymosan, as a potential ligand of CD300b. Phytosphingosine stimulated NO production in inflammatory DCs and promoted neutrophil recruitment in a CD300b-dependent manner. Together, these results suggest that the phytosphingosine-CD300b interaction promotes zymosan-dependent neutrophil accumulation by inducing NO production by inflammatory DCs and that CD300b may contribute to antifungal immunity.